Intermediates for 3-hydrazino-1,2,8,9-tetraazophenalenes

ABSTRACT

3-Hydrazino-1,2,8,9-tetraazaphenalenes optionally substituted in the 4, 5, 6, 7 and/or 9 positions and their salts are cardiovascular agents and are prepared from 3-thiono-2,3-dihydro1,2,8,9-tetraazaphenalenes. Representative embodiments are 3hydrazino-1,2,8,9-tetraazaphenalene and 3-hydrazino-9-phenyl1,2,8,9-tetraazaphenalene.

United States Patent Doehelet al.

INTERMEDIATES FOR 3-HYDRAZINO- l ,2,8,9-TETRAAZOPHENALENES Inventors: Karl J. Doehel, Ossining, NY.

10562; John E. Francis, Pleasantville, NY. 10578 Assignee: Ciba-tleiy Corporation, Ardsley,

Filed: April 6, 1970 Appl. No.: 31,068

Related US. Application Data Division of Ser. No. 7l5,555, March 25, 1968, Pat. No. 3,578,665, Continuation-impart of Ser. No. 583,980, Oct. ,3, 1966, abandoned, Continuation-impart of Ser. No. 539,303, April l, 1966, abandoned, Continuation-impart of Ser. No. 445,762, April 5, i965, abandoned.

US. Cl. ..260/250 A, 424/250 Int. Cl. ..C07d 51/08, C07d 51/04 Field of Search ..260/250 A [451 Sept. 12, 1972 [56] References Cited UNITED STATES PATENTS 3,560,499 2/1971 Doebel et al. ..260/250 3,560,500 2/1971 Doebel et al. ..260/250 3,562,268 2/1971 Doebel et al. ..260/250 Primary Examiner-Nicholas S. Rizzo Attomey-Karl F. Jorda, Bruce M. Collins and Martin J. Spellman, Jr.

[5 7] ABSTRACT 12 Claims, No Drawings INTERMEDIATES FOR 3-HYDRAZINO- 1 ,2,8,9- TETRAAZOPHENALENES CROSS REFERENCE Ser. No. 583,980 being a continuation-in-part of Ser. Nos. 539,303 and 445,762. I

DETAILED DESCRIPTION The present invention pertains tov 3-hydrazinol,2,8,9-tetraazaphenalenes of the formula:

. IvRNHNT y R I N I I. wherein R is hydrogen, (lower)alkyl, phenyl or phenyl(lower)- alkyl;

R is hydrogen or phenyl; R is hydrogen, chloro, bromo, hydroxy, (lower)-alkoxy, carboxy or nitro, and

R is hydrogen or phenyl and to the acid addition and quaternary salts thereof.

The term alkyl" and derivations thereof such as alkoxy denotes a straight or branched hydrocarbon chain. When qualified by the designation (lower)," such chain will containup to and including six carbon atoms. Illustrative of such alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl, pentyl, hexyl, and the like, while illustrative of such alkoxy groups are methoxy, ethoxy, propoxy, butoxy and the like. I

The compounds of thepresent I invention are identified herein as derivatives of the novel parent tricyclic nucleus l,2,8,9-tetraazaphenalene which is assigned the following numbering The 3-hydrazino-l,2,8,9-tetraazaphenalenes of the instant invention are cardiovascular agents, in particular, blood-pressure lowering agents. They also manifest coronary and peripheral vascular dilation properties, and anti-inflammatory activity.

These compounds can be administered parenterally or orally in any of the usual pharmaceutical forms including tablets, capsules, powders, suspensions, solutions, syrups and the like, including sustained release preparations which can be compounded by any of the known procedures.

A particularly preferred group of compounds are those of Formulal wherein R is hydrogen.

The compounds of the present invention are prepared in a first embodiment via treatment of a 3- thiono-2,3-dihydro-l,2,8,9-tetraazaphenalene of Formula II with a hydrazine of the formula RNl-INH;

III N T I A II NIINII,

N- In It:

N in II The reaction is carried out with aqueous hydrazine I or 100 percent hydrazine in an organic solvent such as ethanol, methyl cellosolve, ,diethylene glycol or diglyme, generally at reflux temperature until the reaction is complete, a' period generally of from 16 to 48 hours. v j I In a second embodiment,'the compounds of Formula l are prepared through treatment of a 3-chloroor 3- bromo-l ,2,8,9-tetraazaphenalene of Formula III with a hydrazine of the formula: RNI-INl-l:

N RIICH=NNHT wherein R is indolyl, pyridyl, styryl or the group:

in which each of R, R and R is hydrogen, amino, al-

koxy, chloro, fluoro, alkanoylamido, cyano or alkyl.

The hydrazine of Formula I is thus reacted with an aromatic aldehyde to form the corresponding hydrazone, generally a high melting substance, which is easily isolated and which upon treatment with strong acid such as hydrochloric acid regenerates the hydrazine starting material of Formula I. In addition to thus being valuable intermediates for purification purposes, the compounds of Formula IV are cardiovascular agents having properties similar to those described for the compounds of Formula I. Thus they are blood pressure lowering agents which manifest coronary and peripheral vascular dilation properties.

The 3-thiono-2,3-dihydro-l ,2,8,9 tetraazaphenalenes of Formula II and the 3-halol,2,8,9-tetraazaphenalenes of Formula Ill are obtained from 3-keto-2,3-dihydro-l ,2,8,9-tetraazaphenalenes of Formula V:

Thus for example, treatment of a 3-keto-2,3-dihydrol,2,8,9-tetraazaphenalene of Formula V with phosphorus pentasulfide in refluxing pyridine yields the corresponding thiono analog of Formula [1.

Alternatively, treatment of the 3-keto-2,3-dihydro compound of Formula V with phosphorus oxychloride or phosphorus pentachloride and phosphorus oxychloride or phosphorus oxybromide or phosphorus pentabromide and phosphorus oxybromide, generally at elevated temperatures, e.g., at reflux, for twenty or more hours, yields the corresponding 3-halo compound which is then treated with an appropriate hydrazine to yield a compound of Formula I.

The valuable intermediate 3-keto-2,3-dihydrol,2,8,9-tetraazaphenalenes of Fonnula V can be prepared by several methods. In a first embodiment, a 3-aldehydo phthalic acid, a 3-benzoylphthalic acid, or a functional equivalent of either is treated with a hydrazine of the formula RNl-lNl-l to yield the corresponding 8-carboxy-l (2H )-phthalazinone:

coon coon 0 COOH RANHNHQ N-R R R3 l N -c=o v1 v i 7 Generally the reaction is easily executed as through heating the reactants, optionally in the presence of a solvent such as alcohol, at temperatures up to about 80 C.

In addition to the 3-carbonylphthalic acids of Formula VI, various functional equivalents may be employed. For example, in place of the aldehyde function there can be a dibromomethyl group, as in 3-dibromomethyl phthalic acid. The aldehyde group can also be in the form of an acetal. Alternatively, or in addition, the carboxylic acid groups can be esterified or be in the form of an anhydride, as in the case of 2-dibromomethyl-6- carbomethoxybenzoic acid or 3-dibromomethylphthalic anhydride. The 3-aldehydoor 3-benzoylphthalic acid can also be in its tautomeric form, a 3-hydroxy-7- carboxy phthalide, optionally bearing a phenyl group in the 3-position. in these phthalides the hydroxy group in the 3-position can be etherified or replaced by a halogen atom, especially bromo while the carboxylic acid function can be esterified or in the form of an acid halide, as in the case of 3-bromo-7-chlorocarbonylphthalide.

Thus, among the functional equivalents of the phthalic acids of Formula VI are compounds of the formulas:

u om (10X com m R I o A R2 X wherein A is an aldehyde, benzoyl, dibromomethyl or dialkoxy-methyl group;

each of R and R taken together are a divalent oxygen atom; and

X is hydroxy, alkoxy, chloro or bromo. These various intermediates can be easily prepare via conventional methods. For example, when the known 3-methylphthalic anhydride or a substituted analog thereof is treated with at least two equivalents of N-bromosuccinimide under the influence of light, a 3- dibromomethyl phthalic anhydride is obtained. Treatment of this anhydride with aqueous base such as sodium hydroxide at from 25 to followed by acidification with a mineral acid yields 3-aldehydophthalic acid (which in its tautomeric form is 3-hydroxy-7-carboxyphthalide). Esterification under conventional techniques, e.g., an alkanol and a catalytic amount of acid, yield the dialkyl 3-aldehydophthalate (which in its tautomeric form is 3-alkoxy-7-carboalkoxy-phthalide).

Likewise bromination of a 2-methyl-6-carbalkoxybenzoic acid (obtained through selective esterification of 3-methylphthalic acid) yields the corresponding 2- dibromomethyl-6-carbalkoxybenzoic acid.

In addition a 7-carboxyphthalide (obtained from a 3- bromomethylphthalic anhydride in a fashion analogous to that described above, i.e., successive treatment with base and acid) is converted to the corresponding 7- halo-carbonylphthalide as with phosphorus oxychloride, thionyl chloride or the like and halogenated in the 3-position with a N-halosuccinimide to yield a 3- halo-7-halocarbonylphthalide.

The l(2l-l)phthalazinones of Formula VII wherein R is hydrogen can also be converted to the corresponding l(2l-l)phthalazinones wherein R is alkyl or phenylalkyl through alkylation, as with an alkyl or phenylalkyl chloride or bromide in aqueous inorganic base or in a (lower)alkanol in the presence of alkali hydroxide or alkali alkoxide. In this conversion it is generally preferable to first esterify the free carboxy group in the 8-position, as through formation of the acid chloride and treatment with an alkanol.

The 8-carboxy-1(2H)phthalazinone or more preferably an acid chloride or ester thereof, is next I treated with hydrazine to yield the 3-keto-2,3-dihydro 1,2,8,9-tetraazaphenalene of Formula V. This reaction with hydrazine generally requires somewhat more drastic conditions than are needed in the fonnation of the 8-carboxy-1(2H)phthalazinone itself, e.g., temperatures above 80, longer reaction times, etc. Accordingly, the 1(2H)phthalazinone is heated with hydrazine at reflux temperatures for at least 72 hours. Optionally, a high boiling solvent such as methyl cellosolve, diglyme or triglyme can be present.

Alternatively, the phthalic acids of Formula V1 or the functional equivalents thereof discussed above, can be converted directly to the 3-keto-2,3-dihydro-l,2,8,9- tetraazaphenalene of Formula .V wherein R is hydrogen in essentially one manipulative step, through the use of at least two molar equivalents of hydrazine. This reaction is conducted at elevated temperatures generally above 80, optionally in the presence of a solvent such as methyl cellosolve.

1t will be appreciated that A the 1,2,8,9- tetraazaphenalenes of the present invention can exist in a wide variety of tautomeric forms and all such forms are deemed to be within the scope of the present invention.

. Also included within the scope of the present invention are the acid addition salts of these novel tetraazaphenalene derivatives, obtained via the conventional methods. Typical salts thus include those derived from hydrochloric, hydrobromic, sulfuric, phosphoric, methanesulfonic, acetic, lactic, succinic, embonic, malic, maleic, aconitic, phthalic, tartaric and the like acids. Quaternary salts derived from alkyl halides are also within the scope of this invention.

The following examples, presented for illustration and not limitation, will serve to further typify the nature of the present invention; In these examples temperature is expressed in degrees Centigrade.

EXAMPLE 1 3-Keto-2,3-Dihydro-1 ,2,8 ,9-Tetraazaphenalene A mixture of 3-methy1phtha1ic anhydride (81 g'), N- bromosuccinimide (182 g), benzoyl peroxide (40 mg) and carbon tetrachloride (1500 ml) is irradiated and heated at reflux by a 100 Watt insertion-type ultraviolet lamp under stirring and exclusion of moisture. After the mixture becomes brick red, an additional 40 mg of benzoyl peroxide is added, Illumination at reflux is carried out during 24 hours. The mixture is cooled and filtered free of succinimide and the filtrate is evaporated in vacuo. The residual yellowish brown solid is dissolved in hot ether, treated with decolorizing charcoal and filtered. Addition of hexane to the filtrate affords the crystalline product, a,a-dibromo-3- methylphthalic anhydride, m.p. 90.593 C. in 72 percent yield. Two recrystallizations from ether-hexane yield colorless needles melting at 93-9S C.

Calcd. for

, C H Br O C, 33.78; H, 1.26; Br, 49.92;

Found: 33,66; 1,20; 49.41.

A suspension of a,a-dibromo-3-methylphthalic anhydride (80 g) in ethanol (500 ml) is treated with a solution of 100 percent hydrazine hydrate (100 ml) and water (100 ml) dropwise under stirring and cooling. A white suspension forms. After the addition, the

temperature is raised gradually to reflux, whereupon the white suspension disappears and a yellow precipitate forms. After 88 hours at reflux, the mixture is cooled, filtered and the first crop of product is washed with water and ethanol and dried in vacuo. The mother liquors are evaporated in vacuo, dissolved in 500 ml of glacial acetic acid and heated under reflux for 18 hours. The mixture is cooled and filtered and a second crop of the product obtained. The overall yield of 3-keto-2,3-dihydro-1,2,8,9-tetraazaphenalene, m.p. 347, is 25.7. g, or 55 percent of theory. The product is recrystallized from 3 liters of boiling dimethylformamide and obtained as a yellow powder which, on heating, forms a microcrystalline solid at 229-270" C. and melts above 350 C.

Calcd: C, 58.06; H, 3.25; N, 30.09;

Found: 57.92 3.58; 30.28;

' EXAMPLE 2 3-Keto-2,3-Dihydro-1,2,8 ,9-Tetraazaphenalene a. 8-Carboxy-1(2H)phtha1azinone. a,a-Dibromo- 3-methylphthalic anhydride (40 g) is added in portions to a hot solution'of 2N sodium hydroxide (500 ml) with stirring. After. 10 minutes, the clear solution is rendered strongly acidic with concentrated hydrochloric acid and heated for one-half hour at The solution is evaporated to dryness in vacuo and the residue is then dissolved in hot water (600 ml), treated withdecolorizing charcoal and filtered. After three days at 5 C., the colorless filtrate yields 21.3 g (88 percent) of colorless blocks of 3-hydroxy-7-carboxyphthalide, m.p. 165.51

68.5 C., obtains after two further crystallizations from water. Calcd. for

C H O C,55.68; H,3.12;

Found: 55.98; 2.99.

A mixture of 3-hydroxy-7-carboxyphthalide (30.2 g)

% hydrazine hydrate (50 ml) and water (100 ml) is heated under reflux for 16 hours. The yellow mixture which forms is then rendered acidic under stirring with dilute hydrochloric acid. The pasty mass which forms is filtered, washed with water and dried at 100 in vacuo, 8-Carboxy-1 (2H)phthalazinone, m.p. 300.5-306 C, is obtained in a yield of 99 percent, and is recrystallized once from glacial acetic acid, m.p. 303.5-306 C.

Calcd: C, 56.84; H, 3.18; N, 14.73;

Found: 57.02; 3.15; 14.65.

8-Carboxy-1(2H)phthalazinone can also be directly obtained from a,a-dibromo-3-methylphthalic anhydride by refluxing with hydrazine hydrate, either 100 percent hydrazine hydrate in chloroform or 50 percent aqueous hydrazine hydrate in ethanol.

b. 3-Keto-2,3-dihydro-1 ,2,8,9-tetraazaphenalene. To a cold stirring suspension of 8-carboxy-l(2 H)phthalazinone (7.6 g) in absolute methanol (100 ml) is added an ethereal solution of diazomethane (aprox. 0.1 mole). The mixture is stirred under moisture exclusion overnight at room temperature and then evaporated in vacuo. The resultant yellow powder (8.9 g) is triturated with cold dilute sodium carbonate and filtered. Recrystallization of the dried solid (6.25 g), m.p. 205-208 C., from methanol yields pure 8-carbomethoxy-1(2H)phthalazinone, m.p. 207-209 C.

Calcd: C, 58.82; H, 3.95 N, 13.72;

Found: 58.77; 3.99; 13.86.

A solution of 8-carbomethoxy-l(2H)phthalazinone (1.02 g) in 100 percent hydrazine hydrate ml) and absolute ethanol ml) is heated at reflux for 110 hours, then is cooled and filtered. The precipitate is washed with water, then methanol and dried in vacuo. The yield of 3-hydroxy-2,3-dihydro-l ,2,8,9- tetraazaphenalene, m.p. 350 C. is 0.78 g, or 84 percent of theory EXAMPLE 3 3-Keto-9-Methyl-2,3-Dihydro-1,2,8,9- Tetraazaphenalene a. 7-Carboxyphthalide. Crude 3- bromomethyl(phthalic anhydride (47.6 g) prepared according to the procedure of Albisetti, Barney, Cairns and Winberg, U.S. Pat. No. 2,729,622, is dissolved in ethanol (100 ml) and aqueous 2N sodium hydroxide (500 ml) and heated for 15 minutes at 80. The pale yellow solution is cooled, rendered acidic with concentrated hydrochloric acid, heated at 80 for one hour andrefrigerated overnight. The acid (35.4 g, m.p. 166-9 C) separates in buff crystals. Two recrystallizations from methanol yield colorless blocks, m.p. l68.5171C.

Calcd: C, 60.66; H, 3.40; Found: 60.41 3.35. b. 7-Phthalidylcarbonyl chloride. A mixture of 7- carboxyphthalide (38.54 g) thionyl chloride (27 ml) and dry benzene (108 ml) is heated at reflux with exclusion of moisture for 3 hours. The excess solvent and thionyl chloride are removed by distillation in vacuo and the solid residue is recrystallized from benzenehexane. The yield of product, m.p. 9296.5 C, is 30.78 g, or 73 percent of theory.

0. 7-Carbethoxyphthalide. 7-Phthalidylcarbonyl chloride (30.78 g) and absolute ethanol (1845 ml) are heated under reflux under moisture exclusion for 30 minutes. The solvent is partially evaporated, whereupon the first crop of product crystallizes. The mother liquors are evaporated in vacuo to dryness, triturated with ethanol and filtered. The two crops are recrystallized from benzene and 23.1 g (65 percent) of product m.p. 89.5-92.5 C are obtained. Recrystallization from ethanol yields the pure ester, m.p. 90.592 C.

Calcd: C, 64.07; H, 4.89; I Found: 64.10; 4.88.

d. 3-Bromo-7-carbethoxyphthalide. A mixture of 7-carbethoxyphthalide (17.78 g), -bromosuccinimide (15.52 g), carbon tetrachloride (345 ml) and benzoyl peroxide (40 mg) is brought to incipient reflux with stirring and exclusion of moisture and then illuminated with a 250 Watt tungsten lamp. No color change is apparent but after minutes, all of the N-bromosuccinimide has been converted to succinimide. The mixture is cooled, filtered and the filtrate evaporated in vacuo to 25.2 g of amber oil, The infrared spectrum of the oil shows peaks at 1,720 cm" (ester) and 1800 cm (7- lactone).

e. 8-Carbethoxy- 1 (2H )phthalazinone. 3-Bromo-7- carbethoxyphtholide (25.2 g) is dissolved in absolute ethanol (172 ml), whereupon a white precipitate forms. 100 percent l-lydrazine hydrate (17.25 ml) in absolute ethanol (172 ml) is added dropwise with stirring and cooling and the mixture is heated at reflux for 16 hours and then filtered free of the white precipitate. The filtrate is evaporated to dryness in vacuo, triturated with lN l-lCl (150 ml) and filtered. The resulting insoluble yellow precipitate and the filtrate are extracted separately with chloroform. The extracts are combined and concentrated in vacuo to a yellow solid (7.15 g). This crude ester is purified by chromatog raphy over neutral alumina and recrystallized from ethanol to yield the product as colorless blocks, m.p.

l69.5-l71.5C.

Calcd: C,60.54; 11,4.62; N,l2.84; Found 60.54; 4.62; 12.62.

f. 2-Methyl-8-carbethoxy-1(2l-l)phthalazinone. 8- Carbethoxy-l(2l-l)phthalazinone (6 g) is dissolved almost completely in 2N sodium hydroxide (22 ml) and water (22 ml). More water (100 ml) is added, followed by dimethylsulfate (6 ml) dropwise under stirring. An oil forms at first but it slowly crystallizes. After one hour, the acidic solution is basified with 5 ml. of 2N sodium hydroxide. Methylsulfate (1.8 ml) is again added dropwise under stirring and the mixture stirred for 16 hours at room temperature. The white precipitate which forms is collected, washed with cold water and dried in vacuo. The filtrate is made slightly basic and extracted several times with chloroform. Concentration of the chloroform layer yields a pale yellow solid whose infrared spectrum was identical to the first crop of material. The first crop is recrystallized from benzene-cyclohexane with the aid of decolorizing carbon in white needles melting in the range 103.5-l 05.

Calcd. for

C I-1 N 0 C,62.06; H,5.2l; N,l2.07; Found: 62.25; 5.50; 11.98.

The infrared spectrum (chloroform) shows prominent bands at 1735 cm (ester carbonyl) and 1655 cm (amide carbonyl).

Alternatively, intermediates of this type, such as 2- methyl-8-carbomethoxy-(21-1)phthalazinone can be prepared via the following procedure: 8-Carbomethoxy-l(2l-l)phthalazinone (2.04 g) obtained through the use of methanol rather than ethanol in part (c) is dissolved in warm absolute methanol ml) and treated under stirring with sodium methoxide (0.60 g), whereupon a solution forms. Methyl iodide (0.63 ml) is added and the whole refluxed under exclusion of moisture for one hour, then stirred at room temperature for 16 hours. The orange-yellow solution is evaporated to small volume, treated with warm water and filtered. As the filtrate cools, colorless crystals precipitate from it. The product is collected and washed with cold water. This material, m.p. l l5-l2 1.5 is purified by two crystallizations from water whereupon it melts at l25-l 26.

g. 3-Keto-9-methyl-2,3-dihydro-l ,2,8 ,9- tetraazaphenalene. To a solution of hydrazine hydrate (5 ml) in methylcellosolve (20 ml) is added 2-methyl- 8-carbethoxyl (2H)phthalazinone 1.16 g). The whole is stirred at reflux for 26 hours, during which time a yellow solution forms. The solution is filtered hot and the filtrate allowed to cool under refrigeration. The yellow crystals which precipitate are collected, washed with methanol and dried. The mother liquor is evaporated to dryness in vacuo and the residue triturated with hot methanol and filtered. The precipitate is a second crop of the product. The combined material, m.p. 300304 (386 mg) is recrystallized from methyl cellosolve and the pure product obtained in bright yellow needles, melting at 305-306.

Calcd. for 3 C1oHgN40: C, H, N, Found: 59.91; 4.18; 28.12

The infrared spectrum (Nujol) reveals a prominent amide carbonyl peak at 1655 cm".

EXAMPLE 4 3-Keto-9- Ethyl-2,3-Dihydro-l,2,8,9- Tetraazaphenalene 8 -Carbethoxy-1(2l-l)phthalazinone (3.0g) is dis- I solved in 2N sodium'hydroxide (11.0 ml). Water (60 ml) is added, followed by diethylsulfate (4.2 ml) dropwise under stirring. The mixture is stirred 60 hours at chloroform. Thechloroformlayer is dried over sodium sulfate and concentrated in. vacuo. A yellow oil is obtained, which is purified by distillation in a Spaeth apparatus at- 0.03 mm with an air bath temperature of 160. The LR. spectrum of the colorless oily product taken in chloroform reveals strong bands at 1735 cm (ester carbonyl) and 1655 cm (amide carbonyl), thus indicating that the product is 2-ethyl-8-carbomethoxyl(2l-l)phthalazinone. This ester 1.6 g) is suspended in a mixture of hydrazine hydrate (5.7 ml) and methyl cellosolve (23 ml) and heatedat reflux for 96 hours. The resulting yellow solution isevaporated to dryness in vacuo and the yellow residue triturated with methanol and filtered. The precipitate (0.5 g) is recrystallized from water and the pure product obtained as yellow needles, m.p. 21 8-219. Calcd. for

C l-l N 0: C, 61.67; H, 4.71; N, 26.15;

Found: 61.42; 4.79; 26.07. The infrared spectrum (Nujol) shows a strong amide carbonyl band at 1,650 cm.

EXAMPLE 5 3-Keto-9-Phenyl-2,3 Dihydro-1 ,2,8 ,9' Tetraazaphenalene a. 8-Carboxy-2-phenyl-l (2l-l)phthalazinone. A mixture of phenylhydrazine (3.6 ml), 3-hydroxy-7-carboxyphthalide (5.82 g) and glacial acetic acid (100 ml) is heated under reflux for 18 hours. The clear solution is evaporated to dryness in vacuo and the residual solid triturated with methanol and collected. The product (6.97 g), m.p. l97-199, is recrystallized from benzene and a colorless crystalline product, m.p. l97l98, obtained.

Calcd. for

C l'l N 0 C,67.,66; 11,3.79; N, 10.52; Found: 67.28; 3.75; 10.82.

The infrared spectrum (Nujol) shows prominent peaks at 1720 cm (carboxyl group) and 1650 cm" (amide carbonyl).

b. 8-Carbethoxy-2phenyl-l(2H )phthalazinone. To a solution of thionyl chloride (40 ml) in chlorobenzene (150 m1) is added under stirring 8-carboxy-2-phenyl-l(2H)-phthalazinone (24.3 g) and the mixture heated at reflux under moisture exclusion for 2 hours. When the evolution of gas has ceased, the solution is evaporated to dryness in vacuo. The residual white solid (24.7 g)'is treated with absolute ethanol (350 ml) and heated under reflux for 18 hours. The solution is filtered hot and allowed to cool slowly. The ester precipitates in colorless needles, m.p. -l51. This material (23.9 g) is recrystallized from ethanol.

The melting point is unchanged.

Calcd. for

CHI-114N203: C, H, N, Found: 69.08; 4.65; 9.36. c 3-Keto-9-phenyl-2,3-dihydro-1,2,8 ,9-

tetraazaphenalene. A mixture of 2-phenyl-8-carbethoxy-l(2l-l)-phthalazinone (11.76 g), 100 percent hydrazine hydrate (40 ml) and methyl cellosolve ml) is heated at reflux for 25 hours. The yellow solution is filtered and treated with methanol (100 ml) followed by water dropwise under stirring. A flocculerit yellow precipitate forms. The mixture is cooled and the product collected, washed thoroughly with water and ethanol and driedv in vacuo. The solid (4.44 g), m.p. 2546, is recrystallized from methyl cellosolve and obtained as yellow needles, m.p. 255-7. Calcd. for

EXAMPLE 6 3-Keto-9-Benzyl-2,3-Dihydrol ,2,8 ,9- Tetraazaphenalene To a suspension of sodium methoxide (7 g) in dry dimethylsulfoxide (500 ml) is added 3-keto-2,3- dihydro-l,2,8,9-tetraazaphenalene (18.6 g) and the mixture is heated to 60C. Benzyl bromide (14 ml) is added under stirring and the mixture stirred at 60 for 2 hours. The dark mixture is poured into ice-water, stirred for 20 minutes and filtered. The dark brown precipitate is collected, washedwith water, dried and then suspended in ethanol (400 ml). The insoluble tancolored solid is collected (18.3 g) and recrystallized from methyl cellosolve with decolorizing charcoal added. A crop of 5.3 g of solid is obtained on cooling and a second crop (4.1 g) slowly crystallizes from the mother liquor. The combined material is recrystallized three times from ethanol, the product (4.1 g) thus obtained melting at 329-243.

Calcd. for

CHI-112N401 C, H, N, 69.25; 4.54; 20.38. Similarly through the use of methyl iodide there is obtained 3-keto-9-methyl-2,3-dihydrol ,2,8 ,9- tetraazaphenalene, m.p. 289-293 C.

EXAMPLE 7 3-Keto-9-n-Butyl-2,3-Dihydro-l ,2,8 ,9- Tetraazaphenalene To a stirring mixture of 3-keto-2,3-dihydro-l,2,8,9- tetraazaphenalene (55.8 g), sodium methoxide (18 g) and dry dimethylsulphoxide (450 cc) at 60 is added nbutyl bromide (42 g). The mixture is stirred at 60 for 4 hours and then poured into ice-water. The solid which EXAMPLE 8 3-Keto-7-Phenyl-2 ,3-Dihydro-l ,2,8 ,9- Tetraazaphenalene a. 4-Phenyl-8-carboxy-l(2l'l)phthalazinone. 3- Benzoyl-phthalic acid (32.5 g) prepared by permanganate oxidation of 2-methyl-6-benzoylbenzoic acid, hydrazine hydrate (85 ml) and water (145 ml) are heated at reflux for 18 hours. The mixture is cooled and rendered acidic with hydrochloride acid. The said which precipitates is recrystallized from glacial acetic acid to yield 4-phenyl-8-carboxy-1(2l-l)phthal-azinone, m.p. 257-259.

Calcd.for

C I-1 N C,67.66; 11,3.79; N, 10.52; Found: 67.87; 3.68; 10.82.

b. 4-Phenyl-8-carbomethoxy-1(2l-l)phthalazinone. A mixture of 4-phenyl-8-carboxy-l (2H)phthalazinone (19.0 g), thionyl chloride (32 ml) and chlorobenzene (115 ml) is stirred at reflux under moisture exclusion for 3 hours. The solution is concentrated at reduced pressure to a white solid which is dissolved in methanol (300 ml) and heated at reflux for 18 hours. The mixture is cooled and the crystalline ester, m.p. 198-202, collected. This material can be used directly in the following step.

c. 3-Keto-7-phenyl-2,3-dihydro-l ,2,8,9- tetraazaphenalene. A mixture of 4-phenyl-8-carbomethoxy-l(2H)-phthalazinone (18.6 g), hydrazine hydrate (400 cc) and water (100 cc) is heated at reflux for 20 hours. The mixture is cooled and the precipitate is collected, washed with water and recrystallized from methyl cellosolve to yield the product, m.p. above 350 C Calcd. for

C, l-l, N,0: C,68.70; 11,3.85; N,2l.37; Found: Found: 68.89; 3.62; 21.39;

EXAMPLE9 3-Keto-9-( Z-Phenethyl)-2,3-Dihydro-l ,2,8,9- Tetraazaphenalene a. 2-( Z-Phenethyl )-8-carboxy- 1 2H )phth alazinone. To a mixture of anhydrous sodium acetate (28.4 g) glacial acetic acid (1300 ml) and 2-phenethylhydrazine sulphate (26.0 g) is added 3-hydroxy-7-carboxyphthalide (19.4 g). The mixture is stirred at reflux for 18 hours, filtered hot and evaporated to dryness. The residue is triturated with chloroform and the chloroform layer is extracted with 5 percent sodium carbonate solution. The alkaline extracts are cautiously rendered acidic with 6N hydrochloric acid and the material which precipitates is extracted with chloroform. The dried chloroform extracts are evaporated to dryness and the residue is taken up in boiling benzene, filtered and slowly treated with hexane. The white precipitate which forms is collected, washed with hexane and dried. The product (m.p. ll5-123) can be further purified through recrystallizations from ethanol-water. (m.p. l l9-l 22 C). Calcd. for

C H,.,N O C,69.37; l-l,4.79; N,9.52; Found: 69.40; 4.67; 9.48. b. 2-( Z-Phenethyl)-8-carbomethoxy-l (21-1 )phth alazinone. A mixture of 2-(2phenethyl)-8-carboxyl(2l-l)phthalazinone (8.0 g), thionyl chloride (13 ml) and chlorobenzene (60 ml) is heated at reflux with stirring and exclusion of moisture for 2.5 hours. The solution is then evaporated to dryness at reduced pressure and the residue heated with absolute methanol (200 ml) at reflux for 66 hours. The mixture is filtered hot and the filtrate cooled at -20 C overnight. The precipitated product is collected, washed with a little cold methanol, dried and recrystallized from methanol, m.p. ll3-114.

Calcd. for

C, H, N O C,70.l1; l-l,5.23; N,9.09; Found: 70.00; 5.23; 8.95.

c. 3-Keto-9-(2-phen ethyl)-2,3-dihydro-1,2,8 ,9- tetra-azaphenalene. A mixture of 2-(2-phenethyl)-8- carbomethoxy-l(2l-l)phthalazinone (32.5 g), 100 percent hydrazine hydrate (400 cc) and water (70 cc) is stirred at reflux for 20 hours and then cooled. The yellow precipitate is collected, washed thoroughly with water, air dried, and recrystallized twice from chloroform to afford the product, m.p. 203-5.

Calcd. for

C,-,1-l, N 0: C, 70.32; H, 4.86; Found: 70.13; 4.87; 19.33.

EXAMPLE l0 3-Keto-9-lsopropyl-2,3-Dihydro- 1 ,2,8,9- Tetraazaphenalene a. 8-Carbomethoxy-l(2H)phthalazinone. To a suspension of 8-carboxy-l(2l-l)phthalazinone (182 g) in chlorobenzene 1200 cc) is added thionyl chloride (250 cc). This mixture is stirred at reflux with moisture exclusion for four hours, cooled and filtered. The white precipitate is washed with benzene, air dried, and suspended in absolute methanol (1,500 cc). This mixture is heated at reflux under moisture exclusion for 18 hours, cooled to 0 and filtered. The solid thus collected is washed with cold absolute methanol and air dried, m.p. 2l32l5 C.

b. 3-Ket0-9-isopropyl-2,3-dihydrol ,2,8 ,9- tetraazaphenalene. 8-Carbomethoxyl (2 ll)phthalazinone (20.4 g) is suspended in methanol (250 ml) and treated with a mixture of 2-iodopropane (17 g), 1N sodium hydroxide ml) and methanol 100 m1). This mixture is stirred on the steam bath for 3 hours and then evaporated to dryness at reduced pressure. The residue is suspended in a mixture of methanol (50 ml), 100 percent hydrazine hydrate (420 m1) and water ml) and heated at reflux for 66 hours. The mixture is cooled and the yellow solid collected, washed with water and dried. The crude product is triturated with hot chloroform (800 m1), filtered and the filtrate evaporated to dryness at reduced pressure. The product, m.p. 266-268, is recrystallized three times from ethanol, m.p. 258-259.

Calcd. for

3-Thiono-2,3-Dihydrol ,2,8 ,9-Tetraazaphenalene A mixture of 3-keto-2 ,3-dihydro-l ,2,8,9- tetraazaphenalene (44.14 g), phosphorus pentasulfide (58.2 g) and dry pyridine (356 ml) is heated at reflux for 2.5 hours under stirring and exclusion of moisture. The dark red solution is cooled and poured under stirring into one liter of ice-cold saturated salt solution. The mixture is stirred for 1% hours, then filtered and the precipitate washed thoroughly with water and dried at 100 C in vacuo. The orange solid (35.0 g, m.p. 298-320 dec.) is recrystallized once from methyl cellosolve-water (during which operation a small amount of insoluble solid is removed) and once from dimethylformamide-water. The powdery solid melts at 318-32 2 on a block preheated to 250*.

Calcd: C,53.45; 11,299; N, 27.71; Found: -.53.37; 3.00; 1 27.85.

' EXAMPLE l2 3-Thiono-9-Phenyl-2,3-dihydro-l ,2,8,9- Tetraazaphenalene A mixture of 3-keto-9-phenyl-2,3-dihydro-1,2,8,9- tetraazaphenalene (2.6 g), phosphorus pentasulfide (2.5 g) and dry pyridine ml) is stirred for 2% hours under reflux, cooled slightly and poured into ice-cold sodium chloride solution (200 ml). The mixture is stirred for 1% hours and the yellow precipitate which is formed is collected by filtration, washed with water and dried. The solid is recrystallized from ethanol to yield 1.68 g of golden yellow plates, m.p. 232234 C. Calcd. for

Found:

C, 64.72; H, 3.62; N, 20.13; S,

EXAMPLE 13 3-Thiono-9-Methyl-2,3-Dihydro-1 ,2,8,9- Tetraazaphenalene c,55.53; 11,3.73; N, 25.91; S,

EXAMPLE14 3-Thiono-9-Benzyl-2,3-Dihydro-l ,2,8,9- Tetraazaphenalene 3-l(eto-9-benzyl-2,3-dihydro-l ,2,8,9- tetraazaphenalene (2.76 g) is suspended in drypyridine (25 ml) and phosphorus pentasulfide (2.5 g) added under stirring and the mixture stirred at reflux under moisture exclusion for 3 hours. The dark solution is poured into ice-water, whereupon an orange solid precipitates. The mixture is stirred 30 minutes, filtered and the precipitate washed with water and dried. The crude product is recrystallized from methyl cellosolve and obtained as yellow needles (1.7 g), m.p. 27827 9.5

EXAMPLE l5 3-l-lydrazino-1 ,2 ,8 ,9-Tetraazaphenalene A mixture of 3-thiono-2,3-dihydro-l ,2,8,9- tetraazaphenalene (30 g) and percent hydrazine hydrate (500 ml) is refluxed under vigorous stirring for 20 hours. The mixture is cooled, filtered and the yellow precipitate washed with water and dried in vacuo. The free base (21.0 g) is suspended in excess 3N hydrochloric acid, filtered free of residual solid and evaporated in vacuo. The residue is triturated with methanol, filtered and recrystallized by dissolution in water followed by addition of methanol and concentrated hydrochloric acid. A further recrystallization from water-concentrated hydrochloric acid yields the product as the dihydrochloride, m.p. 245-248 C (dec.), on slow heating.

Calcd: C, 39.57; H, 3.69;v N, 30.77; Cl,

Found: 39.68; 4.34; 30.78; 25.65.

EXAMPLE l6 3-l-lydrazino-l ,2 ,8 ,9-Tetraazaphenalene Dimethanesulfonate 3-l-lydrazino-l,2,8,9-tetraazaphenalene (2.0 g) is suspended in absolute ethanol (60 ml) and methanesulfonic acid (1.3 ml) in ethanol (20 ml) is added dropwise under stirring. At first, an almost clear solution is formed but after about one-half hour, an orange precipitate forms. The mixture is heated to about 50 C for 15 minutes, cooled and filtered. The product is recrystalized twice from methanol-ether and a constant melting point of 235237 C is obtained.

Calcd: C, 33.67; H, 4.11; N, 21.42; Found: 33.94; 4.40; 21.46.

EXAMPLE l7 3-Hydrazino-9-Benzyl-l ,2,8,9-Tetraazaphenalene Hydrochloride A mixture of 3-thiono-9-benzyl-2,3-dihydro-1,2,8,9- tetraazaphenalene (5.4 g), percent hydrazine hydrate (230 ml) and water (60 ml) is stirred under reflux for 18 hours. The mixture is cooled and the yellow product collected and dried. The solid is suspended EXAMPLE 18 3-l-lydrazino-9-Phenyl-l ,2,8,9-Tetraazaphenalene To a solution of hydrazine hydrate 100 percent) (54 ml) and water ml) at 8090 is added in small portions with stirring 3-thiono-9-phenyl-2,3-dihydro- 1,2,8,9-tetraazaphenalene (5.6 g). The reaction mixture is heated at reflux for 18 hours and the orange mixture filtered hot. The precipitate is washed repeatedly with distilled water and then taken up in 3N hydrochloric acid. The mixture is washed twice with chloroform and the aqueous acidic layer is treated with charcoal, filtered and the filtrate evaporated at 60 to a small volume. Pale yellow crystals appear. The mixture is cooled and the crystals of product are collected. Yield: 3.05 g. Evaporation of the mother liquor to dryness yields an additional 2.4 of crystals.

This material is further purified via the following conversion. The combined material is taken up in 60 ml of cold water, filtered free of some insoluble solid and placed in a 3 necked 300 cc flask equipped with mechanical stirrer, condenser and dropping funnel. An equal volume of ethanol is added and the yellow solution heated to 70 C. Benzaldehyde (9 ml) in ethanol (25 ml) is added, whereupon a bright yellow precipitate forms. Normal sodium bicarbonate solution (20 ml) is added dropwise over a five minute period and the yellow mixture stirred minutes at 70. An additional 40 ml of bicarbonate are added rather quickly, whereupon the precipitate turns orange. The mixture is stirred at 70-80 for 15 minutes and then filtered hot. The precipitate is washed with ethanol and dried in vacuo. The yield of 3-benzylidenehydrazino-9- phenyl-l,2,8,9-tetraazaphenalene as an orange-red solid, m.p. 2102l5 C is 4.4 g. When recrystallized from methyl cellosolve, the intermediate is obtained in dark red plates melting in the range 2l6222 C.

The 3-benzylidenehydrazino compound (17.9 g) is suspended in a large excess of 6N hydrochloric acid and boiled until a clear solution is obtained. The solution is evaporated to dryness at reduced pressure and the residue recrystallized twice from methanol-ether to afford 3-hydrazino-9-phenyl-1,2,8,9-tetraazaphenalene as a yellow crystalline product, m.p. 176-178.

EXAMPLE 19 3-Hydrazino-9-Methyl- 1 ,2,8,9-Tetraazaphenalene 1n a 1-liter flask equipped with reflux condenser and mechanical stirred is placed 100 percent hydrazine hydrate (162 ml) and water (60 ml) and the solution heated to 90. 3-Thiono-9-methyl-2,3-dihydro-l,2,8,9- tetraazaphenalene (6.48 g) is added and the mixture stirred 20 hours at reflux. The mixture is filtered hot to remove some red solid and the filtrate evaporated invacuo. The residual yellow solid is taken up in 3N hydrochloric acid (400 ml) filtered to remove insoluble yellow solid and evaporated to dryness in vacuo. The residue is dissolved as well as possible in water and refiltered. Evaporation of the filtrate in vacuo yields the product as a pale yellow solid residue.

The solid is purified by dissolving it in water (50 ml) and ethanol (50 ml) and treating it at under mechanical stirring with benzaldehyde (15 ml) in ethanol (50 ml). Water 25 ml) is added, followed by 1N sodium bicarbonate ml) and the mixture stirred for 5 minutes at 70. More 1N sodium bicarbonate is added and the mixture stirred for 10 minutes at reflux. The mixture is cooled and the orange benzylidene hydrazone collected, washed with water and treated with boiling excess 2N hydrochloric acid under stirring until no odor of benzaldehyde remains and a clear yellow solution is obtained (about 5 hours). The solution is cooled, filtered through sintered glass and the filtrate evaporated to dryness in vacuo. The residual solid is thoroughly dried in a dessicator under vacuum over phosphorus pentoxide and then recrystallized from methanol-ether. A second recrystallization from methanol-ether yields 4.4 g of pale yellow crystals which decompose with gas evolution at about 260 Calc. for

C H N QHCI:

Found: 41.89;

C, 41.83; H, 4.21; N, 29.26;

EXAMPLE 2O 3-Phenylhydrazino-9-Phenyl-l ,2,8,9- Tetraazaphenalene a. 3-Chloro-9-phenyl-l ,2,8,9-tetraazaphenalene. To a stirred mixture of phosphorus pentachloride (6.3 g) in phosphorus oxychloride (40 ml) is added finely powdered 3-keto-9phenyl-2,3-dihydro-l ,2,8 ,9- tetraazaphenalene (7.8 g). The mixture is stirred at reflux for 165 minutes under moisture exclusion, then poured cautiously into ice, and rendered alkaline under cooling with 20 sodium hydroxide solution. The fine yellow precipitate which forms is collected and washed with water, stirred for one-half hour in 600 ml of warm (50) water and again filtered. The precipitate is recrystallized from ethanol and 5.4 g of yellow crystals,

m.p. 225-228, obtained. The infrared spectrum shows no trace of carbonyl absorption as seen in the starting material. Calc. for

C, H C1N C, 64.18; 11,3.24; N, 19.96; Cl

12.63; Found: 64.21; 3.08; 19.70; 12.67. b. 3-Phenylhydrazino-9-phenyl-1,2,8 ,9-

tetraazaphenalene. A mixture of 3-chloro-9-phenyl- 1,2,8,9-tetraazaphenalene (1.0 g) and phenylhydrazine (25 ml) is stirred at C. for 20 hours. Most of the phenylhydrazine is then removed by distillation at reduced pressure. The residue is triturated with aqueous sodium bicarbonate and then taken up in chloroform. The chloroform solution is dried over sodium sulfate, concentrated in vacuo to about 6 ml and passed through a column of basic alumina. Fractions are checked by thin layer chromatography of small C H N C, 71.57; H, 4.58; N, 23.85; Found: 71.64; 4.11; 23.50.

EXAMPLE 21 3-l-lydrazino-9-Phenyl-1 ,2,8,9-Tetraazaphenalene A mixture of 100 percent hydrazine hydrate ml), methyl cellosolve (30 ml) and 3-chloro-9-phenyll,2,8,9-tetraazaphenalene (2 g) is stirred for 4 hours at reflux, during which time a yellow solution is obtained. This is filtered hot and the filtrate treated with water (30 ml) and cooled overnight. The yellow precipitate which has formed is collected, washed with water and dried. The crude 3 hydrazino-9-phenyl-1,2,8,9- tetraazaphenalene (1.4 g) then obtained is suspended in 3N hydrochloric acid, filtered, the filtrate treated with charcoal and refiltered. The yellow filtrate is evaporated in vacuo at 60 to a yellow-red foam. This foam is taken up in water and washed with chloroform. The aqueous acidic layer is evaporated in vacuoand a pale yellow solid (0.85 g) obtained. This material may then be purified through formation and hydrolysis of 3- benzylidene-hydrazino-9-phenyl- 1 ,2,8,9- tetraazaphenalene in a fashion analogous to that described in example 18.

. EXAMPLE 22 3-Hydrazino-7-Phenyl-l ,2,8,9-Tetraazaphenalene By treating 3-keto-7-phenyl-2,3-dihydro-1,2,8,9- tetraazaphenalene (5 g) with phosphoryl chloride (27 m1) and phosphorus pentachloride (4 g) at reflux, evaporating the mixture and isolating the solid obtained upon quenching an acetone solution of the residue in ice-water, there is obtained 3-chloro-7-phenyl-l ,2,8,9-tetraazephenalene, m.p. 278-288 A mixture of 3-chloro-7-phenyl-l ,2,8,9- tetraazaphenalene (8.3 g), hydrazine hydrate (71 ml) and water ml) is heated at reflux for 24 hours. The mixture is cooled and filtered and the precipitate collected, washed thoroughly with water and suspended in dilute hydrochloric acid. The mixture is filtered and evaporated to dryness at reduced pressure. The residue is taken up in water, filtered and evaporated to dryness. The residual solid is triturated with a mixture of absolute ethanol and ether to yield the dihydrochloride of 3-hydrazino-7-phenyll ,2,8 ,9-tetraazaphenalene, m.p. 2 l0--2l5 (dec.). The product may be further purified through formation of the hydrazone, as described in EXAMPLE 23.

EXAMPLE 23 9-Benzylidenehydrazino-7-Phenyl- 1 ,2,8,9- Tetraazaphenalene To a stirred solution of 3-hydrazino-7-phenyl-l ,2,8,9 -tetraaz,aphenalene dihydrochloride (1.62 g) in methanol (10 ml) at 60 is added benzaldehyde (0.6 ml) in methanol (10 ml). One normal aqueous sodium bicarbonate solution (5 ml) is next added and the mixture is stirred at reflux for 10 minutes. An additional 5 ml of bicarbonate are added and the mixture is filtered hot, the precipitate is washed with methanol and water, dried, and recrystallized from aqueous methyl cellosolve to yield the product, m.p. above 350.

EXAMPLE 24 3-(m-Nitrobenzylidenehydrazino)-1 ,2,8,9- Tetraazaphenalene 3-Hydrazinol ,2,8,9-tetraazaphenalene dihydrochloride (1.4 g) in water (10 ml) and ethanol (10 ml) is heated to C, and a solution of mnitrobenzaldehyde (0.75 g) in ethanol (10 ml) added with stirring. An orange color develops at once. Molar sodium bicarbonate solution (5 ml) is added and the solution is refluxed 5 minutes. An orange-red precipitate develops. Addition of another 5 ml of 1N sodium bicarbonate solution, followed by 15 minutes at reflux, results in. the formation of a thick red precipitate. The material is collected from the cooled mixture, washed "with water and ethanol and dried in vacuo. The yield of material, m.p. 350, is 1.54 g or 92 percent of theory. Two recrystallizations from dimethylformamide yield analytically pure material, m.p. 350 C.

Calcd: C, 57.65; H, 3.33; N, 29.42; Found: 57.57; 3.57; 29.23.

EXAMPLE 25 In a similar fashion to that described in Example 24, the following compounds are .prepared from the appropriate aldehydes:

3-(p-cyanobenzylidenehydrazino)-1 ,2,8,9- tetraazaphenalene, m.p. above 350 3-cinnamylidenehydrazino-1 ,2,8,9- tetraazaphenalene, m.p. 235-239 3-( 3-indolylmethylidenehydrazino)-1 ,2,8,9- tetraazaphenalene, m.p. above 350 3-( 3 ,4-dimethoxybenzylidenehydrazino)-1,2,8,9- tetraazaphenalene, m.p. 235237 3-(4-acetamidobenzylidenehydrazino)-1,2,8,9- tetraazaphenalene, m.p. above 350 3-(3,4-dichlorobenzylidenehydrazino)-1,2,8 ,9- tetraazaphenalene, m.p. above 350 3-(2-picolylidenehydrazino)-1,2,8,9- tetraazaphenalene, m.p. 25725 8 3-( 4-dimethylaminobenzylidenehydrazino 1 ,2,8,9- tetraazaphenalene, m.p. 274-276 3-( 3,4,5 ,-Trimethoxybenzylidenehydrazino)- l ,2,8 ,9- tetraazaphenalene, m.p. 265267 and 3-benzylidenehydrazinol ,2,8 ,9- tetraazaphenalene, color change (orange to yellow) 265-267; decomp. at 3 30-3 38.

What is claimed is:

1. A compound of the formula:

"T if wherein R is hydrogen, (lower)alkyl, phenyl or phenyl(lower)alkyl;

R is hydrogen or phenyl;

R is hydrogen, chloro, bromo, hydroxy, (lower) alkoxy or nitro; and

X is oxygen or sulfur.

2. The acid addition salts of a compound according to claim 1.

3. A compound according to claim 1 wherein R is hydrogen, (lower)alkyl, phenyl or benzyl; R is hydrogen; and R is hydrogen.

4. The compound according to claim 1 wherein said compound is 3-oxo-2,3-dihydro-l ,2,8,9- tetraazaphenalene or a tautomer thereof.

5. The acid addition salts of the compound of claim 4 with acids.

6. The compound according to claim 1 wherein said compound is 3-thiono-2,3-dihydro-1,2,8,9- tetraazaphenalene or a tautomer thereof. 

2. The acid addition salts of a compound according to claim
 1. 3. A compound according to claim 1 wherein R1 is hydrogen, (lower)alkyl, phenyl or benzyl; R2 is hydrogen; and R3 is hydrogen.
 4. The compound according to claim 1 wherein said compound is 3-oxo-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 5. The acid addition salts of the compound of claim 4 with acids.
 6. The compound according to claim 1 wherein said compound is 3-thiono-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 7. The acid addition salts of the compound of claim
 6. 8. The compound according to claim 1 wherein said compound is 3-oxo-9-methyl-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 9. The compound according to claim 1 wherein said compound is 3-oxo-9-phenyl-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 10. The compound according to claim 1 wherein said compound is 3-oxo-9-benzyl-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 11. The compound according to claim 1 wherein said compound is 3-thiono-9-phenyl-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof.
 12. The compound according to claim 1 wherein said compound is 3-thiono-9-methyl-2,3-dihydro-1,2,8,9-tetraazaphenalene or a tautomer thereof. 